Microfluidic devices, including “biochip” arrays, “laboratories on a chip”, ultraminiaturized instruments, and the like, have become widely used in research, development, and testing (including diagnostics). Examples include the study of biological-based processes, such as functional genomics (“DNA microarrays”), proteomics, and the like. Often the underlying principle of these reaction devices is an initial binding event between material on a substrate within the device and material in a solution that is exposed to the substrate. Binding events are often diffusion limited and can be enhanced by mixing. Pre- and post-processing such as washing and elution steps can also benefit from mixing in the device. Procedures not necessarily requiring binding, such as electrophoresis and some types of chromatography, are also being implemented on very small devices, often using integrated circuit technology from microelectronics processing. These and other process areas that have been or may be implemented in microfluidic device formats and which may benefit from mixing or enhanced fluid flow include extraction, resuspension, solvation, emulsification, separation, and detection.
It is difficult to actively mix or control fluid flow in small, microfluidic devices. These devices typically have internal dimensions less than about 50 millimeters and flow velocities typically less than about 10 millimeters per second. For these devices, the Reynolds Numbers encountered are typically less than about one (1), so that flow is smooth and non-turbulent. Viscous laminar flow effects dominate and there are no significant inertial effects. Under these conditions, flow streamlines are parallel. In this domain, mass transfer or exchange across the streamlines typically occurs by diffusion. The detrimental effects of having a diffusion-based system on commercial products are numerous, such as but not limited to a constraint on reducing assay times and difficulty in actively controlling intra-assay precision and accuracy.
It is known that acoustic energy, particularly ultrasonic energy, may be used to effect mixing by multiple processes, including temperature, cavitation, and acoustic streaming. For example, acoustic-based mixing has been shown to improve antibody detection and reduce incubation times. However, in the prior art, ultrasonic mixing is performed with a nonfocused transducer operating in the 20,000 to 40,000 Hz range. The transducer contacts the sample fluid directly, which severely limits practical applications, particularly with microfluidic devices. Moreover, when cavitation bubbles formed in older devices collapse, the bubble nucleation, growth and collapse is not directed, nor controlled device.